This invention relates generally to methods of monitoring the presence and/or concentration of target analytes in an aqueous biological system. More particularly, the invention relates to methods for determining the presence, for example measuring the concentration, of one or more analytes in a transdermally extracted sample. One important application of the invention involves a sampling method for monitoring blood glucose using non-invasive or minimally invasive sampling techniques.
A number of tests are routinely performed on humans to evaluate the amount or existence of substances present in blood or other body fluids. These tests typically rely on physiological fluid samples removed from a subject, either using a syringe or by pricking the skin. One particular test entails self-monitoring of blood glucose levels by diabetics.
Diabetes is a major health concern, and treatment of the more severe form of the condition, Type I (insulin-dependent) diabetes, requires one or more insulin injections per day. Insulin controls utilization of glucose or sugar in the blood and prevents hyperglycemia which, if left uncorrected, can lead to ketosis. On the other hand, improper administration of insulin therapy can result in hypoglycemic episodes, which can cause coma and death. Hyperglycemia in diabetics has been correlated with several long-term effects, such as heart disease, atherosclerosis, blindness, stroke, hypertension and kidney failure.
The value of frequent monitoring of blood glucose as a means to avoid or at least minimize the complications of Type I diabetes is well established. According to the National Institutes of Health, glucose monitoring is recommended 4-6 times a day. Patients with Type II (non-insulin-dependent) diabetes can also benefit from blood glucose monitoring in the control of their condition by way of diet and exercise.
Conventional blood glucose monitoring methods generally require the drawing of a blood sample (e.g., by finger prick) for each test, and a determination of the glucose level using an instrument that reads glucose concentrations by electrochemical or colorimetric methods. Type I diabetics must obtain several finger prick blood glucose measurements each day in order to maintain tight glycemic control. However, the pain and inconvenience associated with this blood sampling, along with the fear of hypoglycemia, has lead to poor patient compliance, despite strong evidence that tight control dramatically reduces long-term diabetic complications. In fact, these considerations can often lead to an abatement of the monitoring process by the diabetic.
The present invention provides a method for sampling an analyte present in a biological system. More especially, the invention provides a method for sampling an analyte present beneath a target skin or mucosal surface of an individual, said method comprising:
(a) accelerating particles into and/or across said target surface, wherein acceleration of said particles into or across the target surface is effective to allow passage of a fluid sample from beneath the target surface to the target surface; and
(b) determining the presence of said analyte in said fluid sample.
The invention also provides use of an inert material for the manufacture of a particulate composition for sampling an analyte present beneath a target skin or mucosal surface of an individual by such a method. The method can be used to determine, for example qualitatively or quantitatively, the presence of an analyte of interest in the biological system. The method can also be used to determine the amount or concentration of the analyte of interest. In addition, the method can be used to continually or continuously measure the concentration of the analyte.
The method entails accelerating particles into and/or across a target surface of the biological system such that the particles allow a quantity of an analyte (e.g., a fluid sample containing or suspected of containing an analyte of interest) to pass from beneath the target surface. The analyte can then be contacted with a sensing apparatus to derive a raw detectable signal therefrom, wherein the raw signal is either indicative of the presence of the analyte, or related to the analyte concentration. If desired, the analyte can be collected from the target surface prior to contact with the sensing apparatus.
Sampling is carried out such that the analyte of interest is transdermally extracted from the biological system. In this regard, the terms xe2x80x9ctransdermal extractionxe2x80x9d and xe2x80x9ctransdermally extractedxe2x80x9d intend any non-invasive, or at least minimally invasive method of using particle delivery techniques to facilitate extraction of an analyte from beneath a tissue surface, across skin or mucosal tissue for subsequent analysis on, or collection and analysis from the surface thereof. The terms further include any such extraction whether or not coupled with application of skin penetration enhancers, negative pressure (vacuum or suction), or other extraction technique.
Analyte (generally within a volume of fluid) which is extracted from the biological system is then either contacted directly with a sensing apparatus for obtaining a raw signal indicative of the presence and/or concentration of the analyte of interest, or collected and then contacted with the sensing apparatus. This raw signal can be obtained using any suitable sensing methodology including, for example, methods which rely on direct contact of a sensing apparatus with the biological system, methods which rely on contact with a collected amount of the extracted analyte, and the like. The sensing apparatus used with any of the above-noted methods can employ any suitable sensing element to provide the raw signal including, but not limited to, physical, chemical, biochemical (e.g., enzymatic, immunological, or the like), electrochemical, photochemical, spectrophotometric, polarimetric, calorimetric, radiometric, or like elements. In preferred embodiments of the invention, a biosensor is used which comprises an electrochemical sensing element.
The analyte can be any specific substance or component that one is desirous of detecting and/or measuring in a chemical, physical, enzymatic, or optical analysis. Such analytes include, but are not limited to, toxins, contaminants, amino acids, enzyme substrates or products indicating a disease state or condition, other markers of disease states or conditions, drugs of recreation and/or abuse, performance-enhancing agents, therapeutic and/or pharmacologic agents, electrolytes, physiological analytes of interest (e.g., calcium, potassium, sodium, chloride, bicarbonate (CO2), glucose, urea (blood urea nitrogen), lactate, and hemoglobin), lipids, and the like. In preferred embodiments, the analyte is a physiological analyte of interest, for example glucose, or a chemical that has a physiological action, for example a drug or pharmacological agent. As will be understood by the ordinarily skilled artisan upon reading the present specification, there are a large number of analytes that can be sampled using the present methods.
Accordingly, it is a primary object of the invention to provide a method for sampling an analyte present in a biological system. The analyte is typically present beneath a target skin or mucosal surface of an individual. The method entails the steps of accelerating sampling particles into and/or across a target surface. Acceleration of the sampling particles into or across the target surface is effective to allow passage of a quantity of the analyte (typically a fluid sample comprising the analyte) from beneath the target surface to the target surface. The sample can contain a diagnostic quantity of the analyte. The presence and/or amount or concentration of the analyte which is so extracted is then determined by direct contact with a sensing apparatus, or the analyte is collected from the target surface and then contacted with a sensing apparatus.
An advantage of the invention is that the sampling process can be readily practiced inside and outside of the clinical setting and without pain.
These and other objects, aspects, embodiments and advantages of the present invention will readily occur to those of ordinary skill in the art in view of the disclosure herein.